Remember me on this computer. Enter the email address you signed up with and we'll email you a reset link. Need an account? Click here to sign up. Download Free PDF. Plasticization and spraying of poly DL-lactic acid using supercritical carbon dioxide: control of particle size Journal of Pharmaceutical Sciences, Kevin M Shakesheff. A short summary of this paper. Download Download PDF. Translate PDF. The phenomenon arises from the high solubility and interaction of the scCO2 in the polymer.
Under these unique conditions, temperature and solvent labile molecules can be mixed efficiently into the liquefied polymer. This process is very different from rapid expansion and antisolvent based techniques that have been previously reported. In this article, we describe a method of controlling particle size during the spray process by introducing a backpressure of N2 in the collecting chamber.
In situ observation of the viscosity of the plasticized polymer indicates that a backpressure of 68 bar or greater is necessary to ensure the production of fine particles. Thus, this process is very different from drug registration there is a need to improve the that of RESS Rapid Expansion of Supercritical method of particle production. Key issues in Solutions , which requires both species to dissolve production are preservation of drug activity in the scCO2.
Howdle Telephone: tional solvent before being precipitated by spray- ; Fax: ; E-mail: steve. In fact, the plasticization process has been shown to occur in high-pressure CO2 at much lower temperatures, below C. The addition of scCO2 significantly lowers the viscosity of the plasticized polymer. This is particularly advantageous for the mixing process described above. After mixing, the contents of the high-pressure autoclave are transferred through an orifice.
If the depressurization process occurs rapidly through the orifice nozzle then small Figure 1. A further Cylinder; B, nitrogen cylinder; C, CO2 feed pump; D, complication or attraction to the technique is that valves; E, mixing vessel; F, collecting chamber; G, the escaping CO2 can influence polymer morphol- pressure gauges; H, thermocouple; I, backpressure ogy, for example generating macroporosity.
If the liquefied mixture is sprayed into a collecting vessel at atmospheric product was dried under vacuum at room tem- pressure, the loss of CO2 from the polymer is too perature for 48 h.
In this article, we 1. The A schematic diagram for the supercritical fluid scientific rationale for the choice of backpressure is apparatus used to prepare PDLLA particles is explored by in situ measurement of polymer vis- shown in Figure 1. The equipment consists of cosity with CO2.
In combination with the growing three main units: a mixing unit, a collecting unit, literature on the use of supercritical fluid mixing and a cooling unit.
Synthesis of PDLLA Once intimate mixing is achieved, the spraying PDLLA was synthesized in bulk using stannous valve is switched on and off repeatedly by a gas octoate [Sn Oct 2] as the initiator and diethylene pressure motor, allowing the fluid mixture to pass glycol DEG as the molecular controller.
The resulting polymer electronic controller. The collecting unit contains was then dissolved in CHCl3, and recovered by a collecting chamber F , a cone nozzle L mou- precipitation in an excess of hexane. The collecting chamber is filled with maintain the same stirrer rate of revolution. This nitrogen prior to the spraying process through the increase in current is related to the increase in feeding system B and D.
We have used a set chamber with liquid nitrogen. There are no com- ber. The data acquisition and control systems mercial devices available to accurately measure employ the Hazard Evaluation Laboratories such data. The isobaric run Fig. The data obtained are by no means was performed at 88 bar with the temperature accurate or absolute, but provide an empirical increasing from 35 to C at a rate of 0.
Our and to evaluate processing conditions. For the measurement of viscosity is based upon the load most promising materials, we undertook a further placed on the motor. The normal load is measured more detailed sieving to generate particle size in air a baseline value mA. If the stirrer is distributions using sieves with more narrowly distributed aperture sizes from 38, 63, 90, , , , , , to mm.
Under these conditions, the plasti- cized polymer can then be sprayed through an orifice, leading to a substantial drop in pressure to yield particles. Figure 3 shows an SEM image of Figure 2. Figure 3. However, on the extensional dimension the size is large and ranged widely from tens of micrometers to several hundred micrometers. Our attempts to make a more particulate sample by manipulating Figure 4.
SEM images of the products generated at the conditions of temperature or pressure of scCO2 54 and 88 bar N2 backpressures; the supercritical in the mixing vessel proved to have no effect upon conditions employed to plasticize the polymer with CO2 in the mixing vessel were set at C and bar.
From Figure 4, it is also clear that the particle Effect of Backpressure on size of sprayed products strongly depends on Particle Size and Morphology N2 backpressure. Samples produced under each Thus, we investigated the effect of spraying the different N2 backpressure were sieved to allow plasticized mixture into a collecting chamber that particle sizing. When a N2 backpressure of 27 or was held at a higher pressure, i.
Nitrogen was chosen as the backpressure of 88 bar Fig. Further, within backpressure gas because the view cell experi- our range of processing, a significant increase in ments have shown that it does not plasticize the average particle size was observed at the lower PDLLA polymer but is miscible with CO2.
For all backpressures. Particle Size and Morphology Figure 4 shows SEM images obtained of particle products generated using different N2 backpres- Having established that a backpressure was sures.
The data clearly demonstrate that particles necessary to produce particulate product, we generated at 54 and 88 bar N2 backpressures are now determined if any variation in the mixing discrete entities compared to the fibrous or plate conditions could further adjust the particle size material in Fig. Most of the particles possess a and morphology.
The logic behind this was that porous morphology that results from the escaping by changing the temperature or pressure of the CO2 forming bubbles that push against the scCO2 in the mixing vessel, the viscosity of the solidifying polymer. Using Figure 5. Comparison of sieving results for the pro- the calibration data Fig.
Further, by isothermally lowering the polymer with CO2 in the mixing vessel were set at pressure further, from 54 to 27 bar, it is clear that C and bar. Note the control of particle size the polymer gets even more viscous and effec- exerted by the backpressure.
The cumulative the particles as they form at the exit of the nozzle particle size distribution generated from precision in the spraying experiments, we can begin to sieving for the products produced at a N2 back- rationalize the particle formation process.
Under this specific the exit orifice of the nozzle in the collecting chamber, the pressure in the polymer drops from bar to the value of the N2 backpressure very rapidly. If we now assume that the effect of the N2 backpressure is to momentarily trap the scCO2 in the polymer, then this will keep the polymer plasticized whilst droplets are formed. This will be the key controlling factor in determin- ing the viscosity of the plasticized polymer at the orifice and the solidification rate of the mixture.
If this is the case, then we should be able to use the isothermal viscosity data derived from the CO2 experiments Fig. Cumulative particle size distribution gen- sprayed particle size and morphology. Note that saturation temperature has pendent of the CO2 pressure above 68 bar. Thus, little effect upon particle size. When the spray limited, the polymer solidifies immediately as it process is carried out at a lower backpressure of exits the orifice, and only thin plates and fibres are 54 bar and 27 bar, the data show that there is an collected.
Saovaros Svasti. Suthat Fucharoen. Thongperm M. Orapan Sripichai. A short summary of this paper. Ann Hematol — DOI The explanation for clinical severities, from nearly asymptomatic to transfu- phenotype variability in this condition is now being sion-dependent thalassemia major. This study investigated explored. Genetic factors that reduce the globin chains severe thalassemia. This finding demonstrates that the genetic combina- thalassemia [2—5].
Sripichai : T. Munkongdee : C. Kumkhaek : S. Svasti : Materials and methods P. Winichagoon : S. Informed consent, which was approved by the institutional O. Sripichai : S. Svasti Department of Biochemistry, Faculty of Science, review board of Mahidol University Thailand , was Mahidol University, obtained from each participant or their parents.
To counts were determined by an automated blood cell minimize transfusion effects on hematologic data, we analyzer Advia Hematology System, Bayer, NY, excluded the assessed subjects whose Hb typing showed USA. Hemoglobin type and quantitation were performed the presence of Hb A. Statistic state Hb level was 3. Group I comprised prevalent. Of this cohort, we found that 7. Among the 81 8. Although the mean age, 9.
However, significant difference for all hematologic parameters. In addition to the imbalance of globin chain thalassemia 1 0. However, in a family study year-old woman.
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